The SGLT2 inhibitor empagliflozin for the treatment of type 2 diabetes mellitus: A bench to bedside review

INTRODUCTION: The treatment of type 2 diabetes mellitus (T2DM) continues to pose challenges for clinicians and patients. The dramatic rise in T2DM prevalence, which has paralleled the rise in obesity, has strained the healthcare system and prompted the search for therapies that not only effectively treat hyperglycemia, but are also weight neutral or promote weight loss. In most clinical situations after diagnosis, patients are advised to adopt lifestyle changes and metformin is initiated to help control blood glucose levels. However, metformin may not be tolerated, or may not be sufficient for those with higher glucose levels at diagnosis. Even among those who have initial success with metformin, the majority eventually require one or more additional agents to achieve their treatment goals. Because T2DM is a progressive disease, the requirement for combination treatment escalates over time, driving the need for therapies with complementary mechanisms of action. METHODS AND RESULTS: Online public resources were searched using “empagliflozin”, identifying 32 articles in PubMed, and 12 abstracts presented at the 2013 American Diabetes Association meeting. Peer-reviewed articles and abstracts describing preclinical studies and clinical trials were retrieved, and relevant publications included in this review. Trials registered on clinicaltrials.gov were searched for ongoing empagliflozin studies. CONCLUSION: The sodium–glucose co-transporter 2 (SGLT2) inhibitors are of great interest since they provide a novel, insulin-independent mechanism of action. The SGLT2 inhibitor empagliflozin has demonstrated promising pharmacodynamic and pharmacokinetic properties. In clinical trials, empagliflozin has demonstrated a good efficacy and safety profile in a broad range of patients with T2DM, and appears to be an attractive adjunct therapeutic option for the treatment of T2DM. Ongoing trials, including patients with T2DM and comorbidities such as hypertension, are expected to provide important additional data, which will further define the role of empagliflozin in a growing movement toward individualized approaches to diabetes care. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13300-014-0063-1) contains supplementary material, which is available to authorized users

Electron tunneling time measured by photoluminescence excitation correlation spectroscopy

The tunneling time for electrons to escape from the lowest quasibound state in the quantum wells of GaAs/AlAs/GaAs/AlAs/GaAs double-barrier heterostructures with barriers between 16 and 62 Å has been measured at 80 K using photoluminescence excitation correlation spectroscopy. The decay time for samples with barrier thicknesses from 16 Å (≈12 ps) to 34 Å(≈800 ps) depends exponentially on barrier thickness, in good agreement with calculations of electron tunneling time derived from the energy width of the resonance. Electron and heavy hole carrier densities are observed to decay at the same rate, indicating a coupling between the two decay processes

Carrier lifetimes in ion-damaged GaAs

Photoluminescence excitation correlation spectroscopy has been used to measure the dependence of carrier lifetime on the H+ ion implantation dose in GaAs. For doses greater than 1×10^12 cm^−2 the carrier lifetime is inversely proportional to the ion dose. The minimum lifetime measured was 0.6±0.2 ps for a dose of 1×10^14 cm^−2. Most important, there is no sign of saturation of carrier lifetime with ion dose down to this lifetime, thus still shorter lifetimes should be achievable with increased ion dose

Highly electronegative metallic contacts to semiconductors using polymeric sulfur nitride

The Schottky barriers formed on n‐ZnS and n‐ZnSe by polymeric sulfur nitride have been compared to barriers formed by Au. Barrier energies as determined by photoresponse, current‐voltage, and capacitance‐voltage methods show that (SN)_x is approximately 1.0 eV higher than Au on n‐ZnS and 0.3–0.4 eV higher than Au on n‐ZnSe. We believe that this is the first report of any metallic contact more electronegative than Au

Continuous monitoring of the lunar or Martian subsurface using on-board pattern recognition and neural processing of Rover geophysical data

The ultimate goal is to create an extraterrestrial unmanned system for subsurface mapping and exploration. Neural networks are to be used to recognize anomalies in the profiles that correspond to potentially exploitable subsurface features. The ground penetrating radar (GPR) techniques are likewise identical. Hence, the preliminary research focus on GPR systems will be directly applicable to seismic systems once such systems can be designed for continuous operation. The original GPR profile may be very complex due to electrical behavior of the background, targets, and antennas, much as the seismic record is made complex by multiple reflections, ghosting, and ringing. Because the format of the GPR data is similar to the format of seismic data, seismic processing software may be applied to GPR data to help enhance the data. A neural network may then be trained to more accurately identify anomalies from the processed record than from the original record

The size of MRK 231 at 10 µm

A technique is described for obtaining high-sensitivity measurements with high spatial resolution at 10 µm. An application of the method to Mrk 231 confirms the point like nature of the nucleus at 10 µm

HgSe, a highly electronegative stable metallic contact for semiconductor devices

Schottky barriers formed by the highly electronegative substance HgSe on n-ZnS and on n-ZnSe have been characterized by capacitance-voltage and photoresponse measurements. The barriers are about 0.5 eV greater than Au barriers on these n-type substrates. HgSe contacts are stable under ambient conditions and are easily fabricated, making them attractive for device use

A review of UK media coverage of physical activity associated with the publication of special issues in a high-impact medical journal

Objectives: The media is a substantial vehicle for conveying public health messages to the public. This study examined the extent to which the publication of special issues in a high-impact medical journal in 2012 and 2016 generated media interest in physical activity and health in the UK and explored the main issues that were reported. Study design: This is a systematic narrative review of print media. Methods: Relevant print news articles were identified by searching Factiva and Google News. The timeframe of each search was 2 weeks, using the publication date of each special issue as the anchor point. Overall, 20 articles were included in the analysis for 2012 and 37 articles for 2016. Results: The news media coverage was encouraging for the profile of physical activity and health. In 2012 and 2016, common themes included the benefits of physical activity and the risks of being inactive, comparisons between mortality rates from physical inactivity and smoking and the recommended volume of physical activity to benefit health. Conclusions: The profile given to an issue through prestigious scientific publication is one of the levers for community attention and policy change. Efforts are needed to further use the media for improving policy, practice and public awareness, which are antecedents to population health change

Lyman alpha absorption lines from mini pancakes

[Abridged abstract:] Recent numerical simulations show that many \lyal absorption lines of column densities \nha \la 10^{15} cm$^{-2}$ are produced in transient, mini pancakes. Such pancakes are modeled here, approximating the initial perturbation leading to the formation of the pancake as a single sinusoidal wave. The density and temperature profiles of the gas in the pancake are determined for $z_c \sim 3$, where $z_c$ is the collapse redshift. The \lyal absorption line profiles for a line of sight through the pancake are then calculated. The absorption lines in general have wings signifying bulk motions in the gas. It is shown that the deviation from a single Voigt profile is large for small H I column density lines, in which the effect of bulk motions is large. For lines with \nha > 10^{13} cm$^{-2}$, high temperature tend to wash out the signatures of bulk motion. The analytical modeling of mini pancakes associated with \lyal forest lines --- with 10^{13} \la \nha \la 10^{15} cm$^{-2}$---gives the corresponding mass scales. It is shown here that, for typical values of cosmological parameters, absorption lines with \nha \sim 10^{14} cm$^{-2}$ correspond to structures with baryonic mass of $M_b \sim 10^{10}$ M$_{\odot}$ with an overdensity of $\sim 10$ at $z \sim 3$. The value of \nha can change by a factor $\sim 3$ in the course of evolution of the pancake in time. It is also shown that there is an upper limit to \nha from a pancake due to the slow recombination rate and the importance of collisional ionization at high temperatures. Mini pancakes do not give rise to \lyal lines with \nha \ga 10^{14.5} cm$^{-2}$, for \j21=1 and $\Omega_{IGM} \sim 0.03$.Comment: Latex with aaspp4.sty (25 pages), 6 figures, Accepted for publication in The Astrophysical Journa

Radial Redshift Space Distortions

The radial component of the peculiar velocities of galaxies cause displacements in their positions in redshift space. We study the effect of the peculiar velocities on the linear redshift space two point correlation function. Our analysis takes into account the radial nature of the redshift space distortions and it highlights the limitations of the plane parallel approximation. We consider the problem of determining the value of \beta and the real space two point correlation function from the linear redshift space two point correlation function. The inversion method proposed here takes into account the radial nature of the redshift space distortions and can be applied to magnitude limited redshift surveys that have only partial sky coverage.Comment: 26 pages including 11 figures, to appear in Ap